Endothelial dysfunction is thought to play a key role in the pathogenesis of peripheral arterial disease (PAD). Interestingly, PAD is much more prevalent in the lower extremities than the upper extremities. It has been hypothesized that elevated blood pressure in the lower extremities during upright posture may account for these regional differences in the distribution of PAD. This is supported by evidence of a link between elevated blood pressure and atherosclerosis. Accordingly, the primary aim of the present proposal is to test two hypotheses: 1) Endothelium-dependent relaxation is attenuated with elevated blood pressure; and 2) Atherosclerosis is accentuated with elevated blood pressure. To address these aims, a model of aortic coarctation will be utilized to induce a blood pressure gradient similar but opposite to that of an upright human. Endothelium-dependent and -independent relaxation will be measured in the brachial and femoral arteries of coarctated and control swine. In addition, eNOS protein content will be assessed by immunoblots and immunohistochemistry techniques in the brachial and femoral arteries of coarctated and control animals. Lastly, atherosclerotic lesions will be assessed using histological analysis in conjuction with the Stary scale. [unreadable] [unreadable]